ABSTRACT
Compounds 9 and 13 were synthesized, and their structures and stereochemistry were elucidated by spectroscopic methods. In competition binding experiments, specific [(3)H]-PGE(2) binding was significantly displaced by compound 9 and, to a lesser extent, by 13, in a dose-dependent manner. The biological properties of compound 9 were studied on HL-60 cells, and several effects were found related to those of PGE(2). Compound 9 increases c-fos mRNA level as does PGE(2) and antagonizes TPA-induced terminal differentiation.
Subject(s)
4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/chemical synthesis , Dinoprostone/metabolism , 4-Butyrolactone/chemistry , 4-Butyrolactone/pharmacology , Binding, Competitive , Cell Differentiation/drug effects , Cell Survival/drug effects , Dinoprostone/chemistry , HL-60 Cells , Humans , Proto-Oncogene Proteins c-fos/biosynthesis , Proto-Oncogene Proteins c-fos/genetics , RNA, Messenger/biosynthesis , Radioligand Assay , Stereoisomerism , Structure-Activity Relationship , Tetradecanoylphorbol Acetate/pharmacologyABSTRACT
The biological activity of compound 9 obtained by introducing an alpha-methylene-gamma-butyrolactone group into 3-(4-hydroxyphenyl)propionic acid, 1, was studied for possible effects on HL-60 cells, murine splenocytes, and human peripheral mononuclear cells (PBMC). 9 induced apoptosis in the HL-60 cell line and has a clear capacity to inhibit proliferation induced in murine splenocytes and PBMC by different mitogenic agents with no apparent toxic side effects. 9 was synthesized from 1, and its structure and stereochemistry were elucidated by spectroscopic methods.